Yesterday ASH was able to bring readers, even before it hit the news wires, news of a new study which provides the missing link (or "smoking gun") in the proof that tobacco smoke causes lung cancer.

Below are excerpts from two articles in today's news about the study, the first from the NEW YORK TIMES, and the second from the Associated Press. Both quote ASH.


A team of researchers says it has found a direct scientific link between smoking and lung cancer, a discovery that adds yet another piece to the already substantial evidence that tobacco smoking is a cause of cancer.

The findings, published today in the journal Science, report the first evidence from the cell biology level linking smoking to lung cancer. The scientists say a chemical found in cigarette smoke has been found to cause genetic damage in lung cells that is identical to the damage observed in many malignant tumors of the lung.

The findings reported today establish the long-missing link, in the opinion of experts in the field of cancer genetics, and may also play a role in pending litigation about smoking illnesses and passive smoking.

"This paper absolutely pinpoints that mutations in lung cancer are caused by a carcinogen in cigarette smoke," said Dr. John Minna, a researcher at the University of Texas Southwestern Medical Center. "It is the smoking gun that makes the connection."

John Banzhaf, a professor of law at Georgetown University who is familiar with laws and lawsuits that deal with smoking, said the new research would have profound consequences, both in the courtroom and in everyday life.

"This is very important in imposing liability on the cigarette industry and in protecting nonsmokers from secondhand smoke," said Mr. Banzhaf, who is executive director of ASH, for Action on Smoking and Health, a nonprofit anti-smoking group.

Mr. Banzhaf said the latest study would be a powerful weapon for eliminating smoking from those public places that still allow it. "We're moving to ban smoking even in bars, the last bastion," he said.

And he predicted that the research's pinpointing of a specific mechanism for lung cancer would be a severe blow to the tobacco industry in court, where until recently it had been all but impervious to lawsuits from people claiming that they had become ill from smoking.

In the paper published today in Science, researchers from the University of Texas M.D. Anderson Cancer Center in Houston and the Beckman Research Institute of the City of Hope in Duarte, Calif., studied the effects of a cigarette-smoke ingredient on a gene known as p53.

The gene is vital to the body's well-being because it acts to suppress the runaway growth of cells that lead to tumors. When p53 genes are damaged, the body becomes much more susceptible to cancer. Dr. Vogelstein said that problems with the p53 gene are related to half of all human cancers and are found in up to 70 percent of lung cancers.

A critical factor in the research was the knowledge that, in lung cancers, most of the p53 defects, or mutations, occur at three specific points, or "hot spots," along the DNA molecule. DNA, for deoxyribonucleic acid, is the molecule that carries the hereditary information of living cells. Directed by Dr. Gerd Pfeifer of the Beckman Institute and Dr. Moon-shong Tang at M. D. Anderson, the scientific team exposed human lung cells to the chemical BPDE, a powerful carcinogen that is produced in the body from the breakdown of benzo[a]pyrene, a chemical in tobacco smoke.

Two researchers, Dr. Mikhail Denissenko and Dr. Annie Pao, examined the p53 gene and found that molecules of BPDE had bound chemically to the p53 DNA at precisely the three points that had already been identified as mutational hot spots in lung cancer.

Paul Recer, TOBACCO SMOKE DAMAGES KEY GENE, Associated Press 10/18/96

Researchers have found parts of a key gene in human lung cells that are damaged by tobacco smoke, a finding which they say establishes a specific molecular link between smoking and lung cancer.

In a study to be published Friday in the journal Science, researchers at the M.D. Anderson Cancer Center in Houston report that a tobacco carcinogen called BPDE links up with three molecular sites on the P53 gene -- a gene that is critical in the development of cancer.

``In essence, our study provides a direct link between a defined cigarette-smoke carcinogen and human cancer mutations,'' Moon-shon Tang, the lead author of the study, said in a statement.

A number of earlier studies have linked BPDE from cigarette smoke to lung cancer. Earlier studies also have shown that in most lung cancer the P53 gene is damaged or altered at points in the gene structure that Tang called ``hotspots.'' In the new study, researchers show that BPDE binds, or joins, the P53 gene at exactly those same ``hotspots.''

Though the carcinogen has long been linked to lung cancer, Tang said, ``until now we did not know it binds with the spots on the P53 gene that are associated with lung cancer.'' The ``hotspots'' on the gene also are associated with other types of cancer.

``This is the first specific scientific evidence linking smoking with lung cancer at a molecular level,'' said Dr. Bert Vogelstein, a Johns Hopkins University researcher who first linked the P53 gene with cancer.

The work also provides a powerful new weapon for plaintiffs in lawsuits against tobacco companies, said John Banzhaf, the director of Action on Smoking and Health, a non-profit anti-tobacco group.

``It is confirmation of what we have known before, but it makes it easier now for us to demonstrate in court,'' said Banzhaf. He said the study will enable lawyers to argue that even a small amount of tobacco smoke can cause genetic damage that may lead to cancer and, thus, cigarette smoking should be banned everywhere.

Banzhaf said it also ``helps to close a loophole'' that pro-tobacco lawyers have used. He said some tobacco company lawyers have argued that science has not proven a precise biological process by which cigarette smoke causes lung cancer. ``Now we can identify the mechanism at a molecular level,'' he said.


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